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Reviewed, UniProtKB/Swiss-Prot P31040 (DHSA_HUMAN)

Last modified June 16, 2009. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
    EC=1.3.5.1
Alternative name(s):
    Flavoprotein subunit of complex II
      Short name=Fp
Gene names
Name: SDHA
Synonyms: SDH2, SDHF
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length664 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).

Catalytic activity

Succinate + ubiquinone = fumarate + ubiquinol.

Cofactor

FAD.

Pathway

Carbohydrate metabolism; tricarboxylic acid cycle.

Subunit structure

Component of complex II composed of four subunits: the flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome b560 composed of SDHC and SDHD.

Subcellular location

Mitochondrion inner membrane; Peripheral membrane protein; Matrix side.

Involvement in disease

Defects in SDHA are a cause of complex II mitochondrial respiratory chain deficiency [MIM:252011]; also known as succinate CoQ reductase deficiency. Defects of oxidative phosphorylation give rise to heterogeneous clinical symptoms ranging from isolated organ dysfunction to multisystem disorder. A deficiency of complex II represents a rare cause of mitochondrial encephalomyopathy, leukodystrophy, late-onset optic atrophy and ataxia, myopathy with exercise intolerance, and isolated cardiomyopathy.

Defects in SDHA are a cause of Leigh syndrome (LS) [MIM:256000]. LS is a severe disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions. Ref.3 Ref.6

Miscellaneous

The complex, present in mitochondria, can be degraded to form EC 1.3.99.1, which no longer reacts with ubiquinone.

Sequence similarities

Belongs to the FAD-dependent oxidoreductase 2 family. FRD/SDH subfamily.

Sequence caution

The sequence CAA37886.1 differs from that shown. Reason: Miscellaneous discrepancy. Differs extensively from that shown.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 4343Mitochondrion By similarity
Chain44 – 664621Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
PRO_0000010335

Regions

Nucleotide binding91 – 10616FAD By similarity

Sites

Active site3401Proton acceptor By similarity
Binding site2961Substrate By similarity
Binding site3081Substrate By similarity
Binding site4071Substrate By similarity
Binding site4511Substrate By similarity

Amino acid modifications

Modified residue991Tele-8alpha-FAD histidine By similarity
Modified residue1791N6-acetyllysine By similarity
Modified residue2521Phosphothreonine By similarity
Modified residue4851N6-acetyllysine By similarity
Modified residue4981N6-acetyllysine By similarity
Modified residue5381N6-acetyllysine By similarity
Modified residue5471N6-acetyllysine By similarity

Natural variations

Natural variant331F → V: dbSNP rs1061518.
VAR_049214
Natural variant381D → V: dbSNP rs34635677.
VAR_049215
Natural variant2401E → Q: dbSNP rs1041946.
VAR_049216
Natural variant5241A → V in LS. Ref.3
VAR_016878
Natural variant5541R → W in LS. Ref.6
VAR_002449
Natural variant5551G → E in complex II deficiency and LS. Ref.9
VAR_016879
Natural variant6571V → I: dbSNP rs6962. Ref.2
VAR_049217

Experimental info

Sequence conflict3561G → D in AAD51006. Ref.3
Sequence conflict3981E → D in AAD51006. Ref.3
Sequence conflict5911A → T in AAD51006. Ref.3
Sequence conflict5961D → G in AAD51006. Ref.3
Sequence conflict6001R → Q in AAD51006. Ref.3
Sequence conflict6291Y → F in AAA20683. Ref.2
Sequence conflict6401E → G in AAD51006. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P31040-1 [UniParc].

Last modified November 1, 1995. Version 2.
Checksum: 180B664E3FFD0B34

FASTA66472,692
        10         20         30         40         50         60 
MSGVRGLSRL LSARRLALAK AWPTVLQTGT RGFHFTVDGN KRASAKVSDS ISAQYPVVDH 

        70         80         90        100        110        120 
EFDAVVVGAG GAGLRAAFGL SEAGFNTACV TKLFPTRSHT VAAQGGINAA LGNMEEDNWR 

       130        140        150        160        170        180 
WHFYDTVKGS DWLGDQDAIH YMTEQAPAAV VELENYGMPF SRTEDGKIYQ RAFGGQSLKF 

       190        200        210        220        230        240 
GKGGQAHRCC CVADRTGHSL LHTLYGRSLR YDTSYFVEYF ALDLLMENGE CRGVIALCIE 

       250        260        270        280        290        300 
DGSIHRIRAK NTVVATGGYG RTYFSCTSAH TSTGDGTAMI TRAGLPCQDL EFVQFHPTGI 

       310        320        330        340        350        360 
YGAGCLITEG CRGEGGILIN SQGERFMERY APVAKDLASR DVVSRSMTLE IREGRGCGPE 

       370        380        390        400        410        420 
KDHVYLQLHH LPPEQLATRL PGISETAMIF AGVDVTKEPI PVLPTVHYNM GGIPTNYKGQ 

       430        440        450        460        470        480 
VLRHVNGQDQ IVPGLYACGE AACASVHGAN RLGANSLLDL VVFGRACALS IEESCRPGDK 

       490        500        510        520        530        540 
VPPIKPNAGE ESVMNLDKLR FADGSIRTSE LRLSMQKSMQ NHAAVFRVGS VLQEGCGKIS 

       550        560        570        580        590        600 
KLYGDLKHLK TFDRGMVWNT DLVETLELQN LMLCALQTIY GAEARKESRG AHAREDYKVR 

       610        620        630        640        650        660 
IDEYDYSKPI QGQQKKPFEE HWRKHTLSYV DVGTGKVTLE YRPVIDKTLN EADCATVPPA 


IRSY 

« Hide

References

« Hide 'large scale' references
[1]"Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the flavoprotein (Fp) subunit of liver mitochondria."
Hirawake H., Wang H., Kuramochi T., Kojima S., Kita K.
J. Biochem. 116:221-227(1994) [PubMed: 7798181] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"The cDNA sequence of the flavoprotein subunit of human heart succinate dehydrogenase."
Morris A.A.M., Farnsworth L., Ackrell B.A.C., Turnbull D.M., Birch-MacHin M.A.
Biochim. Biophys. Acta 1185:125-128(1994) [PubMed: 8142412] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-657.
Tissue: Heart.
[3]"Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome."
Parfait B., Chretien D., Roetig A., Marsac C., Munnich A., Rustin P.
Hum. Genet. 106:236-243(2000) [PubMed: 10746566] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LS VAL-524.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Colon.
[5]"Cloning of the flavoprotein subunit of human succinate dehydrogenase."
Malcovati M., Marchetti L., Zanelli E., Tenchini M.L.
(In) Curti B., Ronchi S., Zanetti G. (eds.); Flavins and flavoproteins 1990, pp.727-730, Walter de Gruyter, Berlin (1991)
Cited for: PRELIMINARY PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[6]"Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency."
Bourgeron T., Rustin P., Chretien D., Birch-MacHin M.A., Bourgeois M., Viegas-Pequignot E., Munnich A., Roetig A.
Nat. Genet. 11:144-149(1995) [PubMed: 7550341] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 546-562, VARIANT LS TRP-554.
[7]"Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes."
Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V.
Biochem. J. 383:237-248(2004) [PubMed: 15242332] [Abstract]
Cited for: PROTEIN SEQUENCE OF 76-92 AND 398-418.
Tissue: Adipocyte.
[8]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]"Homozygous Gly555Glu mutation in the nuclear-encoded 70 kDa flavoprotein gene causes instability of the respiratory chain complex II."
Van Coster R., Seneca S., Smet J., Van Hecke R., Gerlo E., Devreese B., Van Beeumen J., Leroy J.G., De Meirleir L., Lissens W.
Am. J. Med. Genet. A 120:13-18(2003) [PubMed: 12794685] [Abstract]
Cited for: VARIANT COMPLEX II DEFICIENCY/LS GLU-555.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

D30648 mRNA. Translation: BAA06332.1.
L21936 mRNA. Translation: AAA20683.1.
AF171030 expand/collapse EMBL AC list , AF171017, AF171018, AF171019, AF171020, AF171021, AF171022, AF171023, AF171024, AF171025, AF171026, AF171027, AF171028, AF171029 Genomic DNA. Translation: AAD51006.1.
BC001380 mRNA. Translation: AAH01380.1.
X53943 mRNA. Translation: CAA37886.1.
S79641 Genomic DNA. Translation: AAB35332.1.
IPIIPI00305166.
PIRJX0336.
S21302.
RefSeqNP_004159.2.
UniGeneHs.440475

3D structure databases

HSSPHSSP built from PDB template 1NEK based on UniProtKB P10444.
SMRP31040. Positions 54-664.
ModBaseSearch...

Protein-protein interaction databases

IntActP31040. 4 interactions.

PTM databases

PhosphoSiteP31040.

2-D gel databases

REPRODUCTION-2DPAGEIPI00305166.

Proteomic databases

PeptideAtlasP31040.
PRIDEP31040.

Genome annotation databases

EnsemblENSG00000073578. Homo sapiens. [Contig view]
GeneID6389.
KEGGhsa:6389.
NMPDRfig|9606.3.peg.24978.

Organism-specific databases

GeneCardsGC05P000271.
H-InvDBHIX0004699.
HIX0024859.
HGNCHGNC:10680. SDHA.
MIM252011. phenotype.
256000. phenotype.
600857. gene.
Orphanet506. Leigh syndrome.
3208. Succinate CoQ reductase deficiency.
PharmGKBPA35605.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP31040.
OMAP31040. TLEFDNL.

Enzyme and pathway databases

BRENDA1.3.5.1. 247.
ReactomeREACT_6305. Electron Transport Chain.

Gene expression databases

BgeeP31040.
CleanExHS_SDHA.
GermOnlineENSG00000073578. Homo sapiens.

Family and domain databases

InterProIPR003953. FAD_bind2_N.
IPR013027. FAD_pyr_nucl-diS_OxRdtase.
IPR003952. FRD_SDH_FAD_BS.
IPR004112. Fum_Rdtase/Succ_DH_flav_C.
IPR011281. Succ_DH_flav_su_fwd.
IPR014006. Succ_Dhase_frdA_Gneg.
[Graphical view]
PfamPF00890. FAD_binding_2. 1 hit.
PF02910. Succ_DH_flav_C. 1 hit.
[Graphical view]
PRINTSPR00368. FADPNR.
TIGRFAMsTIGR01816. sdhA_forward. 1 hit.
TIGR01812. sdhA_frdA_Gneg. 1 hit.
PROSITEPS00504. FRD_SDH_FAD_BINDING. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00139. Succinic acid.
NextBio24820.
SOURCESearch...

Entry information

Entry nameDHSA_HUMAN
AccessionPrimary (citable) accession number: P31040
Secondary accession number(s): Q16395, Q9UMY5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: November 1, 1995
Last modified: June 16, 2009
This is version 112 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents